"Multiple Endocrine Neoplasia Type 1" – What Is It?
Multiple endocrine neoplasia type 1 (MEN1, also known as Wermer syndrome) is a disease caused by mutations, i.e., genetic changes in the MEN1 gene. Those affected by MEN1 have a significantly higher risk of developing tumors of the parathyroid glands associated with hyperparathyroidism (PHPT), tumors of the islet cells of the pancreas, and anterior pituitary neuroendocrine tumors (PitNET). In total, the MEN1 tumor spectrum includes over 20 hormone-producing and non-hormone-producing tumors that can occur in various combinations.
How Is "Multiple Endocrine Neoplasia Type 1" Diagnosed?
Genetic Diagnostics
Genetic testing is recommended for the following people:
- Anyone with two or more MEN1-typical tumors (see below)
- Any person with a MEN1-typical tumor and a first-degree relative with MEN1
- Anyone under 30 years of age with PHPT, precursor pancreatic lesions, or pancreatic islet cell tumor
The diagnosis of “MEN1” is confirmed by detecting a mutation, i.e., a genetic change in the MEN1 gene.
Clinical Diagnostic Criteria
- At least two primary MEN1-typical tumors (e.g., parathyroid tumor, islet cell tumor, or PitNET)
- In family members of a person with proven MEN1, one MEN1-typical tumor is sufficient
MEN1-Typical Tumors Are as Follows:
- Tumors of the parathyroid glands
- Tumors of the anterior pituitary gland (PitNET)
- Well-differentiated hormone-producing tumors of the gastrointestinal tract and pancreas (gastrinoma, insulinoma, glucagonoma, VIPoma)
- Carcinoids (thymus, bronchus, stomach carcinoid)
- Tumors of the adrenal cortex
What Is the Risk of Cancer?
Tumors of the Parathyroid Glands and PHPT
- Most common manifestation of MEN1, occurring in 95% of patients
- The first manifestation occurs in 90% of patients, usually between the ages of 20 and 25
- Characterized by excessive calcium levels in the blood
Well-Differentiated Hormone-Producing Tumors of the Gastrointestinal Tract and Pancreas
- Gastrinomas are tumors that produce the hormone gastrin, which leads to increased hydrochloric acid production in the stomach, which can cause stomach ulcers. The clinical picture is called Zollinger-Ellison syndrome. Gastrinomas occur in around 40% of patients, and the onset is usually before age 40. 25% of patients do not have a relative with diagnosed MEN1.
- Insulinomas are tumors that primarily produce the hormone insulin, which leads to the absorption of sugar into the body’s cells and, thus, to a low blood sugar level. They occur in around 10% of patients. The age of onset for insulinomas caused by MEN1 mutations is around 10 years earlier than for insulinomas that are not caused by a MEN1 mutation.
- Glucagonomas are tumors that produce the hormone glucagon. This hormone provides sugar via various metabolic pathways and thus increases blood sugar levels.
- VIPomas are tumors that produce the hormone VIP (vasoactive intestinal polypeptide), which causes watery diarrhea and low blood potassium levels, among other things.
Tumors of the Adenohypophysis (Anterior Lobe of the Pituitary Gland) = PitNET
- Occurs in 30-55% of patients
- They are the first manifestation in 10% of familial and 25% of non-familial cases
- The most common tumor is the prolactinoma, which produces the hormone prolactin. In women, this can cause milk flow from the breast, menstrual cycle disorders, and sterility. In men, it can lead to impotence, libido disorders, and gynecomastia (growth in the size of the mammary glands).
- GH- and ACTH-producing tumors are less common, and TSH-producing tumors are rare.
Carcinoids
- Thymus, bronchus, and stomach carcinoids occur in about 10% of MEN1 patients and are tumors arising from the neuroendocrine system’s cells.
- Thymus carcinoids are found more frequently in men than women (20:1), and bronchus carcinoids are seen more regularly in women than men.
- Thymic carcinoids in MEN1 are very aggressive and are often fatal.
Adrenal Cortical Tumors
They occur in 20-40% of MEN1 patients and are rarely hormone-producing.
Tumors of the Skin
Angiofibromas, collagenomas, and lipomas often occur in the context of MEN1.
What Is Known About the Development of "Multiple Endocrine Neoplasia Type 1"?
MEN1 is caused by a mutation, i.e., a genetic change in the MEN1 gene. This gene codes for the menin protein, which controls the replication of genetic material in normal metabolism. If the MEN1 gene is present in an altered form, the menin protein can no longer function correctly, and tumors develop.
MEN1 occurs in around one in 20,000-40,000 people and is usually passed on from parents to their children. The inheritance is autosomal dominant. The remaining cases (around 10%) are due to a spontaneous or new mutation, known as a de novo mutation.
Is There Any Form of Treatment Available?
The treatment recommendations for MEN1 depend on the disease in question:
Tumors of the Parathyroid Glands and PHPT
- Complete or partial removal of the parathyroid glands (there is controversy about the extent and timing)
Pituitary Tumors
- Prolactinoma: dopamine agonists (cabergoline, bromocriptine, pergolide and quinagolide)
- GH-producing tumors: surgery, somatostatin analogs
- ACTH-producing tumors: surgical removal of the tumor, radiotherapy
Well-Differentiated Endocrine Tumors of the Gastrointestinal Tract and Pancreas
- Gastrinoma: proton pump inhibitors (PPI), H2 receptor blockers. Surgical procedure is controversially discussed.
- Insulinoma: Surgical therapy
- Gastrinoma: The optimal therapy is controversial and depends primarily on the degree of spread and operability of the tumor
Carcinoids
- If possible, complete removal. Otherwise, long-acting somatostatin analogs, radiotherapy or chemotherapy if necessary
Adrenal Cortical Tumors
- Surgical therapy for tumors > 4cm in diameter, conspicuous radiological signs or significant growth in size
Diagnosis of " Multiple Endocrine Neoplasia Type 1" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Diagnosis of " Multiple Endocrine Neoplasia Type 1" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Medical Measures for Early Detection
Different Screening Tests Are Carried Out for the Various Diseases That Can Occur in the Context of MEN1:
Insulinoma
- Screening start at the age of 5
- Clinic: Unconsciousness, drowsiness, documented hypoglycemia?
- Laboratory (annual): Fasting glucose and insulin
Neuroendocrine Tumors of the Adenohypophysis (PitNET)
- Screening starts at the age of 5
- Clinic: Headaches, visual changes, milk flow, increased growth?
- Laboratory (annual): Prolactin, IGF-1
- Imaging: MRI of the head every 3 years
Parathyroid Adenoma and PHPT
- Screening starts at the age of 8
- Clinical symptoms: back pain, bone pain, weakness, fatigue, psychological changes, kidney stones, nausea, vomiting, constipation, multiple or pathological fractures?
- Laboratory (annually): Calcium
Neuroendocrine Tumors of the Pancreas
- Screening starts at the age of 10
- Clinic: Mostly asymptomatic; VIPoma: Excessive diarrhea?; Glucagonoma: Hyperglycemia, nausea, increased urine output, thirst?
- Laboratory (annually): Possibly chromogranin A, glucagon, proinsulin, pancreatic polypeptide, VIP
- Imaging: MRI of the abdomen annually
Adrenal Adenomas
- Screening starts at the age of 10
- Imaging: MRI of the abdomen (at the same time as imaging of the pancreas)
Thymus, Bronchus, and Stomach Carcinoids
- Screening starts at the age of 20
- Clinic: Usually asymptomatic; flushing, diarrhea, wheezing, edema, or abdominal pain may be indicative
- Imaging: CT/MRI of lungs and abdomen every 1-2 years
Gastrinoma
- Screening starts at the age of 20
- Clinic: Abdominal pain, stomach ulcer, taking proton pump inhibitors?
- Laboratory (annual): Fasting gastrin
Multiple Endocrine Neoplasia Type 1 – What You Can Do Yourself
You Should Pay Attention to This
You should consult a doctor when drowsiness, unconsciousness, weakness, tiredness, cravings, or increased thirst occur. These can be signs of hyperglycemia or hypoglycemia, as well as other hormonal disorders. You should also consult a doctor if you experience gastrointestinal complaints such as diarrhea, nausea, vomiting, and abdominal pain. These should also be clarified immediately if other new abnormalities or complaints occur, such as bone or back pain, headaches, or visual disturbances.
Further Information
Patients can also register for the CPS registry at any time or have this done by the doctors looking after them.
Any further questions?
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